Oxidative stress mediated by lipid metabolism contributes to high glucose-induced senescence in retinal pigment epithelium

Chen, Qingqiu; Tang, Li; Xin, Guang; Li, Shiyi; Ma, Limei; Xu, Yao; Zhuang, Manjiao; Xiong, Qiuyang; Wei, Zeliang; Xing, Zhihua; Niu, Hai; Huang, Wen

doi:10.1016/j.freeradbiomed.2018.10.419

Cited by 66 publications

(38 citation statements)

References 53 publications

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“…Protein carbonylation (PC) is considered to be an important marker of oxidative stress resulting from HFD-induced oxidative damage to proteins [43,44]. Here, we show that an HFD induced a female-specific increase in the PC of WT mice ( Figure 5A) as a possible consequence of the upregulated expression of genes involved in fatty acid oxidation, that is associated with the generation of hydrogen peroxide [45] involved in protein oxidative damage. Unlike WT males, HFD-fed WT females also displayed increased Ho1 protein expression ( Figure 5B,E), which is an indicator of the presence of oxidative stress [46].…”

Section: Discussionmentioning

confidence: 64%

“…For example, both peroxisomal and mitochondrial β-oxidation produce H 2 O 2 and O 2 as byproducts of fatty acid degradation. During nutritional excess, the imbalance in lipid metabolism along with upregulated key genes involved in fatty acid β-oxidation, such as pparα, contributes to increased ROS and oxidative stress [45]. Catalase (Cat), a peroxisomal enzyme, has also been found in cardiac mitochondria with significantly increased activity during HFD feeding [48].…”

Section: Discussionmentioning

confidence: 99%

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Role of Sirt3 in Differential Sex-Related Responses to a High-Fat Diet in Mice

et al. 2020

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Metabolic homeostasis is differently regulated in males and females. Little is known about the mitochondrial Sirtuin 3 (Sirt3) protein in the context of sex-related differences in the development of metabolic dysregulation. To test our hypothesis that the role of Sirt3 in response to a high-fat diet (HFD) is sex-related, we measured metabolic, antioxidative, and mitochondrial parameters in the liver of Sirt3 wild-type (WT) and knockout (KO) mice of both sexes fed with a standard or HFD for ten weeks. We found that the combined effect of Sirt3 and an HFD was evident in more parameters in males (lipid content, glucose uptake, pparγ, cyp2e1, cyp4a14, Nrf2, MnSOD activity) than in females (protein damage and mitochondrial respiration), pointing towards a higher reliance of males on the effect of Sirt3 against HFD-induced metabolic dysregulation. The male-specific effects of an HFD also include reduced Sirt3 expression in WT and alleviated lipid accumulation and reduced glucose uptake in KO mice. In females, with a generally higher expression of genes involved in lipid homeostasis, either the HFD or Sirt3 depletion compromised mitochondrial respiration and increased protein oxidative damage. This work presents new insights into sex-related differences in the various physiological parameters with respect to nutritive excess and Sirt3.

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Section: Discussionmentioning

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Role of Sirt3 in Differential Sex-Related Responses to a High-Fat Diet in Mice

et al. 2020

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“…It is well described in the literature that human retinal pigmented epithelial (RPE) immortalized cells (ARPE-19) exposed to high concentrations of glucose present molecular changes, including a decrease of proliferation, an increase in oxidative stress mediated by ROS production, and augmented lipid droplets and inflammation [85][86][87][88]. These alterations can activate or repress the autophagic flux in RPE cells.…”

Section: Autophagy In Blood Retinal Barriers and Implications On Diabmentioning

confidence: 99%

“…These findings indicated that autophagy was the first defense against oxidative stress in high-glucose conditions. In the longterm, this protective pathway became saturated and inefficient, thus contributing to RPE degeneration in DR [87]. Zhang et al have shown that high glucose concentrations can attenuate the PINK1 and parkin pathways involved in controlling cellular mitophagy.…”

Section: Autophagy In Blood Retinal Barriers and Implications On Diabmentioning

confidence: 99%

Deficient Autophagy Contributes to the Development of Diabetic Retinopathy

Faria¹,

Dátilo²

2020

The Eye and Foot in Diabetes

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Autophagy is a self-degradation process essential to maintain intracellular homeostasis and cell survival, controlling elimination of pathogens, damage to organelles, and nutrient recycling to generate energy. Alterations in autophagic flux have been reported in the mechanisms of several diseases such as neurodegenerative diseases, cancer, diabetes mellitus, and its associated complications. Diabetic retinopathy (DR) is a microvascular complication of diabetes, affecting nearly 30% of diabetic patients. Several pathways are triggered and repressed in the development of DR, and autophagy showed to be relevant in the pathogenesis of this devastating complication. In this chapter, autophagy's involvement in the development and progression of DR will be discussed, mainly in retinal pigmented epithelial cells and retinal microvascular endothelial cells, as well as in Müller cells-the more prominent retinal glial cell.

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“…High concentration of FFA stimulation can increase the production of highly reactive molecular oxygen clusters and reactive nitrogen clusters, which triggers oxidative stress, prolonged imbalance between the production of highly reactive molecules and anti-oxidant effects resulting in tissue damage. These active molecules can directly oxidize and damage DNA, proteins and lipids, and can also act as functional molecular signals, activating a variety of stress-sensitive signaling pathways in cells, which are closely related to insulin resistance and impaired β-cell function [25,26]. Studies have shown that high levels of FFA lead to a large amount of ROS production and oxidative stress, which can also activate stress-sensitive signaling pathways.…”

Section: Disscussionmentioning

confidence: 99%

Pathological mechanism of hidden blood loss after TKA: oxidative stress induced by free fatty acids

Yuan¹,

Yu²,

Qian³

et al. 2020

Preprint

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Objective: To study the correlation between high-level free fat acids（FFA）and red blood cell (RBC) injury and to explore the pathological mechanism of hidden blood loss (HBL) after total knee arthroplasty (TKA).Methods: Perioperative blood indexes were tested in 120 patients underwent unilateral total knee replacement for end-stage knee osteoarthritis. Venous blood samples were collected before operation and 24h, 48h, 72h and 120 h after operations. The changes of FFA, hemoglobin (Hb) and red blood cell number in the blood samples were detected by automatic hematology analyzer. The activity of glutathion peroxidase (GSH-Px), total superoxide dismutase (T-SOD) and hydrogen peroxide (H2O2) levels in the blood were measured. Measurement of reactive oxygen species（ROS）was performed by flow cytometry. Meanwhile, the morphological changes of RBC were analyzed under microscope. Results: Significant hidden blood loss was observed for all patients. The Hb content, RBC and hematocrit（Hct）decreased significantly 24 h after surgery (P <0.05)，while FFA concentration was significantly increased and heteromorphic red blood cells appeared under the microscope. The hemoglobin content decreased to the lowest level at 48 h after the operation (P < 0.01). The change of HBL was the most significant according to the Gross equation with the levels of FFA and ROS in the blood increased significantly and reached the peak at 48 h after operation (P <0.01). Meanwhile, GSH-PX activity, T-SOD activity and H2O2 levels significantly decreased compared with preoperative tested samples (P <0.01). Microscopically, erythrocyte atypia increased significantly with cellular rupture and necrosis identified. After 72 h of operation, ROS concentration began to decline along with FFA concentration. However, the Hb and RBC began to rise. Also, GSH-Px activity, T-SOD activity and H2O2 levels increased as well. All tested parameters tended to return to normal levels five days after surgery.Conclusion: High levels of FFA in blood can induce oxidative stress and damage RBCs, which in turns causes HBL after surgery.

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Oxidative stress mediated by lipid metabolism contributes to high glucose-induced senescence in retinal pigment epithelium

Cited by 66 publications

References 53 publications

Role of Sirt3 in Differential Sex-Related Responses to a High-Fat Diet in Mice

Role of Sirt3 in Differential Sex-Related Responses to a High-Fat Diet in Mice

Deficient Autophagy Contributes to the Development of Diabetic Retinopathy

Pathological mechanism of hidden blood loss after TKA: oxidative stress induced by free fatty acids

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